Intratypic Recombination among Lineages of Type 1 Vaccine-Derived Poliovirus Emerging during Chronic Infection of an Immunodeficient Patient

ABSTRACT We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.

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Circulation of Type 1 Vaccine-Derived Poliovirus in the Philippines in 2001

Journal of Virology ◽

10.1128/jvi.78.24.13512-13521.2004 ◽

2004 ◽

Vol 78 (24) ◽

pp. 13512-13521 ◽

Cited By ~ 101

Author(s):

Hiroyuki Shimizu ◽

Bruce Thorley ◽

Fem Julia Paladin ◽

Kerri Anne Brussen ◽

Vicki Stambos ◽

...

Keyword(s):

Oral Poliovirus Vaccine ◽

Biological Properties ◽

The Philippines ◽

Capsid Region ◽

Population Immunity ◽

Sequence Relationships ◽

Highly Evolved ◽

Healthy Contact ◽

Complete Genomic

ABSTRACT In 2001, highly evolved type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from three acute flaccid paralysis patients and one contact from three separate communities in the Philippines. Complete genomic sequencing of these four cVDPV isolates revealed that the capsid region was derived from the Sabin 1 vaccine strain but most of the noncapsid region was derived from an unidentified enterovirus unrelated to the oral poliovirus vaccine (OPV) strains. The sequences of the cVDPV isolates were closely related to each other, and the isolates had a common recombination site. Most of the genetic and biological properties of the cVDPV isolates were indistinguishable from those of wild polioviruses. However, the most recently identified cVDPV isolate from a healthy contact retained the temperature sensitivity and partial attenuation phenotypes. The sequence relationships among the isolates and Sabin 1 suggested that cVDPV originated from an OPV dose given in 1998 to 1999 and that cVDPV circulated along a narrow chain of transmission. Type 1 cVDPV was last detected in the Philippines in September 2001, and population immunity to polio was raised by extensive OPV campaigns in late 2001 and early 2002.

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Prolonged Replication of a Type 1 Vaccine-Derived Poliovirus in an Immunodeficient Patient

Journal of Clinical Microbiology ◽

10.1128/jcm.36.10.2893-2899.1998 ◽

1998 ◽

Vol 36 (10) ◽

pp. 2893-2899 ◽

Cited By ~ 142

Author(s):

Olen M. Kew ◽

Roland W. Sutter ◽

Baldev K. Nottay ◽

Michael J. McDonough ◽

D. Rebecca Prevots ◽

...

Keyword(s):

Antibody Formation ◽

Vaccine Dose ◽

Polio Eradication ◽

Oral Poliovirus Vaccine ◽

Population Evolution ◽

Codon Positions ◽

Immunodeficiency Syndrome ◽

Common Variable ◽

Common Variable Immunodeficiency Syndrome

VP1 sequences were determined for poliovirus type 1 isolates obtained over a 189-day period from a poliomyelitis patient with common variable immunodeficiency syndrome (a defect in antibody formation). The isolate from the first sample, taken 11 days after onset of paralysis, contained two poliovirus populations, differing from the Sabin 1 vaccine strain by ∼10%, differing from diverse type 1 wild polioviruses by 19 to 24%, and differing from each other by 5.5% of nucleotides. Specimens taken after day 11 appeared to contain only one major poliovirus population. Evolution of VP1 sequences at synonymous third-codon positions occurred at an overall rate of ∼3.4% per year over the 189-day period. Assuming this rate to be constant throughout the period of infection, the infection was calculated to have started ∼9.3 years earlier. This estimate is about the time (6.9 years earlier) the patient received his last oral poliovirus vaccine dose, approximately 2 years before the diagnosis of immunodeficiency. These findings may have important implications for the strategy to eliminate poliovirus immunization after global polio eradication.

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